Non-Alcoholic Fatty Liver Diseasean underestimated epidemic Amir Shlomai MD,PhD Head, Department of Medicine D The Liver Institute Rabin Medical Center, Beilinson Hospital The IASLD semi-annual meeting- Fatty Liver Disease
Outline NAFLD-definition NAFLD- diagnostic dilemmas NAFLD- prevalence estimates NAFLD- recommendation for diagnosis
NAFLD-Terminology NAFLD-Nonalcoholic Fatty Liver Disease NAS (NAFL)- Nonalcoholic steatosis -simple fat (steatosis)- no inflammation, necrosis or fibrosis -Largely benign NASH- Nonalcoholic steatohepatitis -steatosis and injury (steatosis,ballooning,inflammation) -A potentially serious liver disease
NAFLD is the most common etiology for elevated liver function tests NAFLD is becoming the most prevalent liver disease in western world Younnosi et al, Clin Gastro Hepatol 2011
NAFLD is directly linked to obesity and metabolic syndrome Prevalence of NAFLD Prevalence of overweight adults
Natural History of NAFLD
NAFLD- Risk factors for disease progression Rinella ME, JAMA 2015
NAFLD- diagnosis Liver enzymes Ultrasonography / MRI/ MRS Serum biomarkers Liver biopsy
NAFLD-Prevalence studies Variations dependent on detection method Vernon G, Baranova A, Younossi ZM (2011). Systematic review: the epidemiology and natural history of NAFLD and NASH in adults. Alimentary Pharmacology and Therapeutics 34:274-285
NAFLD-Prevalence uncertainty Controversies regarding normal ALT US- sensitivity problems (30% steatosis bar), operator dependent Biopsy diagnostic problems (sample error, non-standardized) Cryptogenic cirrhosis/ burnt-out disease
Current normal ALT threshold underestimates NAFLD prevalence Zelber-Sagi S et al, Liver Int 2006 Shlomai A et al, J Gastro Hepatol 2010
NAFLD-Prevalence uncertainty Controversies regarding normal ALT US- sensitivity problems (30% steatosis bar), operator dependent Biopsy diagnostic problems (sample error, non-standardized) Cryptogenic cirrhosis/ burnt-out disease
NAFLD prevalence based on liver ultrasonography (Dionysos study) 44% 25% 20% 35% Bedogni et al, Hepatology 2005
High prevalence of NAFLD based on liver Bx
NAFLD-Prevalence uncertainty Controversies regarding normal ALT US- sensitivity problems (30% steatosis bar), operator dependent Biopsy diagnostic problems (sample error, non-standardized) Cryptogenic cirrhosis/ burnt-out disease
Sampling variability in liver biopsy of patients with NAFLD Ratziu V et al, Gastroenterology 2005
Striking high NAFLD and NASH prevalence in a middle-aged population (Brook army cohort) Williams et al, Gastroenterology 2011
NAFLD-Prevalence uncertainty Controversies regarding normal ALT US- sensitivity problems (30% steatosis bar), operator dependent Biopsy diagnostic problems (sample error, non-standardized) Cryptogenic cirrhosis/ burnt-out disease
NAFLD as a major etiology of cryptogenic cirrhosis Caldwell et al, Hepatology 1999
Paucity in features of NASH in liver histology of patients with cryptogenic cirrhosis Rinella et al, JAMA 2015
Prevalence studies for NAFLD Variations dependent on geographical area Vernon G, Baranova A, Younossi ZM (2011). Systematic review: the epidemiology and natural history of NAFLD and NASH in adults. Alimentary Pharmacology and Therapeutics 34:274-285
NAFLD incidence and the PNPLA3 gene variants among different ethnicities Williams et al, Gastroenterology 2011 Romeo S et al, Nat Gene 2008
NAFLD diagnosis- how not to miss? EASL CPG 2016
NAFLD diagnosis- who should we screen? Kotronen A et al, Gastroenterology 2009
LEAN NAFLD A newly recognized entity 7% of lean individuals have NAFLD! Younossi et al, Medicine 2012